Aberrant TNF and Notch signaling pathways in schizophrenia and bipolar disorder

Immune pathways, such as the tumor necrosis factor (TNF) pathway and the Notch signaling pathway, are implicated in the pathogenesis of severe mental disorders. In this thesis, Hoseth investigated the TNF and Notch signaling pathways by assessing plasma protein levels and gene expression, as well as associations between these immune pathways and memory, brain volumes, clinical symptoms and psychotropic medication. Patients with severe mental disorders had increased TNF pathway activity and possible attenuated Notch signaling. Circulating leukocytes and cells of the dorsolateral prefrontal cortex are an unlikely source. Increased TNF pathway activity was associated with lower performance on memory tests, while no associations to clinical symptoms were established. Lithium, an important medication in bipolar disorder, may be associated with elements of both the TNF and Notch signaling pathways. Overall, the findings of this thesis support an imbalance in the immune system in severe mental disorders, where increased immune activity is associated with impaired memory performance. Anti-inflammatory drugs may have a role in the treatment of severe mental disorders